PROJECT SUMMARY - LARGE ANIMAL MODELS CORE The Large Animal Models Core was developed at the time of the last competing renewal to address the concern that in vitro cell culture systems and small animal models have not always translated well to solving human health digestive disease problems. The core was designed to provide models more physiologically similar to people. Over the past 5-years, the CGIBD has developed and strengthened a Large Animal Models Core at the NC State University College of Veterinary Medicine focused on medical and surgical technologies in pigs. The overall goal of the core is to provide a cost-effective central resource for Center investigators wishing to understand mechanisms of digestive disease using large animals. This has been particularly successful for CGIBD members interested in esophageal disease, in large part because the pig has proven to be an excellent translational model of diseases such as eosinophilic esophagitis and gastroesophageal reflux disease. The pig esophagus contains esophageal submucosal glands as does the human esophagus, while mice lack these glands. Recent work through the core has helped to establish these glands as a progenitor cell source in the esophagus. Disease models of intestinal ischemia have also continued to be a critical component of the Core, again because pigs are thought to more closely resemble humans in terms of their response to ischemia. Ex vivo (Ussing chambers) and in vitro studies, particularly those involving large animal complex cell culture (2D and 3D) are now being offered to bolster the basic science output from large animals. Furthermore, because of novel ideas related to the interaction of the gastrointestinal tract and the microbiome, we now plan to introduce gnotobiotic pigs as an additional resource. The specific aims of the core are: 1) to provide consultation with Core veterinarians to assess feasibility, logistics and study design; 2) to assist with procurement of animals, and 3) to coordinate animal procedures, including anesthesia, endoscopy, and surgery. The Core directors (Blikslager and Gonzalez) have a demonstrated track record in digestive disease and are board-certified veterinary specialists in surgery. Veterinary board-certified specialists in laboratory animal medicine, internal medicine, anesthesia, and advanced imaging (MRI, CT, nuclear medicine) are readily available from the NC State Veterinary Hospital. Newly renovated facilities funded in large part by an NIH G20 grant are crucial to the Core?s ability to offer medical, surgical and gnotobiotic capabilities adjacent to large animal research housing. Based on funded projects developed with the Large Animal Models Core and CGIBD investigators during the prior funded period, the Core will aim to have 4-6 projects running at any one time. Although the Core currently serves a small number of members, it provides a remarkable scientific impact on their research which would not be possible without the core.